Synergistic effects of BDNF and NT-3 on postnatal spiral ganglion neurons

Mou, Kewa; Hunsberger, Cara L.; Cleary, James M.; Davis, Robin L.

doi:10.1002/(sici)1096-9861(19971006)386:4<529::aid-cne1>3.0.co;2-4

Cited by 80 publications

(62 citation statements)

References 56 publications

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“…Contacts between SGNs and HCs could be quantified in the cochlear explants, providing a unique opportunity to identify regulatory mechanisms for synaptogenesis. BDNF and NT-3, which are known to promote SGN survival and neurite outgrowth (Pirvola et al 1992;Lefebvre et al 1994;Ernfors et al 1995;Malgrange et al 1996;Fritzsch et al 1997a;Hegarty et al 1997;Mou et al 1997), promoted the formation of pre-and postsynaptic markers of the afferent synapse, in agreement with a previous study (Wang and Green 2011).…”

Section: Discussionsupporting

confidence: 86%

Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons

Tong

Brugeaud

Edge

2013

JARO

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Regeneration of synaptic connections between hair cells and spiral ganglion neurons would be required to restore hearing after neural loss. Here we demonstrate by immunohistochemistry the appearance of afferent-like cochlear synapses in vitro after co-culture of de-afferented organ of Corti with spiral ganglion neurons from newborn mice. The glutamatergic synaptic complexes at the ribbon synapse of the inner hair cell contain markers for presynaptic ribbons and postsynaptic densities. We found postsynaptic density protein PSD-95 at the contacts between hair cells and spiral ganglion neurons in newly formed synapses in vitro. The postsynaptic proteins were directly facing the CtBP2-positive presynaptic ribbons of the hair cells. BDNF and NT-3 promoted afferent synaptogenesis in vitro. Direct juxtaposition of the postsynaptic densities with the components of the preexisting ribbon synapse indicated that growing fibers recognized components of the presynaptic sites. Initiation of cochlear synaptogenesis appeared to be influenced by glutamate release from the hair cell ribbons at the presynaptic site since the synaptic regeneration was impaired in glutamate vesicular transporter 3 mutant mice. These insights into cochlear synaptogenesis could be relevant to regenerative approaches for neural loss in the cochlea.

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Section: Discussionsupporting

confidence: 86%

Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons

Tong

Brugeaud

Edge

2013

JARO

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“…An initial dose-response analysis suggested optimal concentration ranges of 10-20 ng/ml for BDNF and NTF3, and 100-200 ng/ml for LIF (data not shown) that were consistent with previous reports (Lefebvre et al, 1994;Marzella et al, 1997;Mou et al, 1997;Whitlon et al, 2006;Zheng et al, 1995). Each of the three growth factors alone significantly improved the survival of spiral ganglion neurons over four days in culture (Table 1).…”

Section: Responsiveness Of Cultured Spiral Ganglion Neurons To Exogensupporting

confidence: 89%

Survival and stimulation of neurite outgrowth in a serum-free culture of spiral ganglion neurons from adult mice

et al. 2007

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We have developed a reliable protocol for the serum-free dissociation and culture of spiral ganglion neurons from adult mice, an important animal model for patients with post-lingual hearing loss. Pilot experiments indicated that the viability of spiral ganglion cells in vitro depended critically on the use of Hibernate medium with B27 supplement.With an optimized protocol, we obtained 2 · 10 3 neurons immediately after dissociation, or about one-fifth of those present in the intact spiral ganglion. After four days in culture, 4% of the seeded neurons survived without any exogenous growth factors other than insulin. This yield was highly reproducible in five independent experiments and enabled us to measure systematically the numbers and lengths of the regenerating neurites.Furthermore, the survival rate compared well to the few published protocols for culturing adult spiral ganglion neurons from other species. Enhanced survival and neurite outgrowth upon the addition of brain-derived neurotrophic factor and leukemia inhibitory factor demonstrated that both are potent stimulants for damaged spiral ganglion neurons in adults. This responsiveness to exogenous growth factors suggested that our culture protocol will facilitate the screening of molecular compounds as potential treatments for sensorineural hearing loss.3

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“…Previous studies on cultured SGN have primarily focused on culturing embryonic and neonatal tissue (Malgrange et al, 1996;Mou et al, 1997;Whitlon et al, 2006;Zhai et al, 2004). There are, obviously, substantial differences between immature and adult tissue and this will inevitably influence the results.…”

Section: Discussionmentioning

confidence: 99%

Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro

Wei

Jin

Järlebark

et al. 2006

Developmental Neurobiology

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ABSTRACT:The inner ear spiral ganglion is populated by bipolar neurons connecting the peripheral sensory receptors, the hair cells, with central neurons in auditory brain stem nuclei. Hearing impairment is often a consequence of hair cell death, e.g., from acoustic trauma. When deprived of their peripheral targets, the spiral ganglion neurons (SGNs) progressively degenerate. For effective clinical treatment using cochlear prostheses, it is essential to maintain the SGN population. To investigate their survival dependence, synaptogenesis, and regenerative capacity, adult mouse SGNs were separated from hair cells and studied in vitro in the presence of various neurotrophins and growth factors. Coadministration of fibroblast growth factor 2 (FGF-2) and glial cell line-derived neurotrophic factor (GDNF) provided support for long-term survival, while FGF-2 alone could strongly promote neurite regeneration.Fibroblast growth factor receptor FGFR-3-IIIc was found to upregulate and translocate to the nucleus in surviving SGNs. Surviving SGNs formed contacts with other SGNs after they were deprived of the signals from the hair cells. In coculture experiments, neurites extending from SGNs projected toward hair cells. Interestingly, adult mouse spiral ganglion cells could carry out both symmetric and asymmetric cell division and give rise to new neurons. The authors propose that a combination of FGF-2 and GDNF could be an efficient route for clinical intervention of secondary degeneration of SGNs. The authors also demonstrate that the adult mammalian inner ear retains progenitor cells, which could commit neurogenesis. '

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Synergistic effects of BDNF and NT-3 on postnatal spiral ganglion neurons

Cited by 80 publications

References 56 publications

Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons

Regenerated Synapses Between Postnatal Hair Cells and Auditory Neurons

Survival and stimulation of neurite outgrowth in a serum-free culture of spiral ganglion neurons from adult mice

Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro

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